The past decade has seen a burgeoning of interest in the biology of the pancreatic islets of Langerhans. The surge in activity is driven in large measure by the rapid increase in the incidence of diabetes, and the critical role of failure of the insulin secreting cells (beta-cells) within the pancreatic islets in the pathogenesis of both major forms of the disease. This symposium will focus specifically on mechanisms of beta-cell failure in type 2 diabetes, which is fast becoming an epidemic disease world-wide (estimated prevalence in the United States alone, 18 million people). Beta-cell failure is now recognized as the event that triggers the transition from pre-diabetes/metabolic syndrome to full-blown type 2 diabetes. Major advances have occurred in our understanding of fundamental beta-cell biology, mechanisms of loss of function and loss of beta-cell mass in type 2 diabetes, and development of new strategies for enhancing beta-cell survival and function in diabetic animals and humans. These advances deserve careful review and discussion in the form of a Keystone symposium to which we expect to attract the very best scientists in the field. These recent advances in knowledge have occurred based on contributions of academic and industrial contributors alike, and our meeting plan includes projected invitations to key contributors from both sectors. The meeting will be divided into three major sections: A) Review of recent progress in understanding of basic beta-cell biology, including mechanisms of fuel-stimulated insulin secretion and the role of receptor-mediated processes in potentiation of fuel-driven responses; B) Mechanisms of beta-cell dysfunction and destruction in response to metabolic fuel imbalance, including the roles of hyperlipidemia, hyperglycemia, and stress responses; C) Targets for improvement of beta cell function and new technological approaches. In sum, we believe that this program will be a timely and valuable contributor to advancement of a research Diabetes Mellitus has increased in epidemic proportions all over the world, affecting in one way or another almost every ethnic and racial group. Although our knowledge on Insulin Action has enormously increased in the last few decades, this is not the case with our understanding of what makes a beta cell fail, the main determinant of clinical diabetes. Until we have a better understanding on what regulates insulin release and what makes these beta cells stop working, it will be very difficult to improve current diagnostic and therapeutic tools. We think that this meeting will provide a forum for comprehensive discussions in the field of islet biology hand in hand with extensive programs in health education, and hopefully change the impact of this disease on our society.